Wolf D A, Hermeking H, Albert T, Herzinger T, Kind P, Eick D
Institute für Klinische Molekularbiologie und Tumorgenetik, GSF Forschungszentrum für Umwelt und Gesundheit, München, Germany.
Oncogene. 1995 Jun 1;10(11):2067-78.
The p130 protein is a recently cloned member of the retinoblastoma protein family. We show here that transformation of NIH3T3-L1 fibroblasts (L1 cells) by the simian virus 40 large T antigen (LTAg) depends on the disruption of DNA binding complexes between transcription factor E2F and p130. LTAg binds to the pocket region of p130 in vivo and disrupts the E2F-p130 complexes. E2F-p130 complexes are present only in quiescent L1 cells and disappear at the G1/S phase boundary concomitantly to induction of DNA synthesis and expression of the E2F-regulated cdc2 gene. p130 is a substrate of cyclin-dependent kinase 2 (Cdk2) in vitro and associates with a Cdk in vivo which is activated upon serum stimulation in late G1. Overexpression of p130 inhibits cdc2 promoter activity and entry of quiescent L1 cells into S phase. The results demonstrate that p130 is negative regulator of cell cycle progression which is specifically targeted by LTAg during cell transformation.
p130蛋白是视网膜母细胞瘤蛋白家族中最近克隆出的成员。我们在此表明，猿猴病毒40大T抗原（LTAg）对NIH3T3-L1成纤维细胞（L1细胞）的转化依赖于转录因子E2F与p130之间DNA结合复合物的破坏。LTAg在体内与p130的口袋区域结合并破坏E2F-p130复合物。E2F-p130复合物仅存在于静止的L1细胞中，并在G1/S期边界消失，同时伴随着DNA合成的诱导和E2F调控的cdc2基因的表达。p130在体外是细胞周期蛋白依赖性激酶2（Cdk2）的底物，在体内与一种Cdk结合，该Cdk在G1晚期受到血清刺激时被激活。p130的过表达抑制cdc2启动子活性以及静止L1细胞进入S期。结果表明，p130是细胞周期进程的负调节因子，在细胞转化过程中是LTAg的特异性作用靶点。
